Primary Biliary CirrhosisPhase 2EPICSNCT03112681
Study to Evaluate Safety, Tolerability and Efficacy of Saroglitazar Mg in Patients With Primary Biliary Cholangitis
A Phase 2 study testing Saroglitazar magnesium 2 mg and Saroglitazar magnesium 4 mg in people with Primary Biliary Cirrhosis, run by Zydus Therapeutics Inc. at 9 sites in United States.
Trial summary
prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability and efficacy of saroglitazar magnesium 2 mg, 4 mg in Patients with Primary Biliary Cholangitis (PBC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- Saroglitazar magnesium 2 mg and Saroglitazar magnesium 4 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 9 sitesUnited States
- Study dates
- 18 Aug 2017to 7 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females, between 18 and 75 years of age, inclusive.
- a) Patients on therapeutic doses of Ursodeoxycholic acid (UDCA) for ≥12 months and stable therapy for ≥3 months prior to enrolment.
- OR b) Patients who are unable to tolerate UDCA, and did not receive UDCA for at least 3 months from the date of screening.
- History of confirmed Primary Biliary Cholangitis Diagnosis, based on American Association for the Study of Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice Guidelines; [Lindor 2009; EASL 2009], as demonstrated by the presence of at least≥2 of the following 3 diagnostic factors:
- History of elevated Alkaline Phosphatase levels for at least 6 months prior to Screening Visit 1
- Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
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- Liver biopsy consistent with PBC.
- ALP ≥1.67x upper limit of normal (ULN) at Visit 1 and Visit 2 and with < 30% variance between the levels from Visit 1 to Visit 2.
- Contraception: Female patients must be postmenopausal, surgically sterile, or if premenopausal, agree to use ≥ 1 effective method of contraception during the trial. Effective methods of contraception are considered to be Hormonal (e.g., contraceptive pill, patch, intramuscular implant or injection); or Double barrier method, i.e., (a) condom (male or female) or (b) diaphragm, with spermicide; or Intrauterine device (IUD); or Vasectomy (partner).
- Must provide written informed consent and agree to comply with the trial protocol.
Who cannot join
- Consumption of >3 units of alcohol per day (>21 units per week) if male and >2 units of alcohol per day (>14 units per week) if female for at least 3 consecutive months in the last 5 years (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor).
- History or presence of other concomitant liver diseases including:
- Hepatitis B or C virus (HCV, HBV) infection
- Primary sclerosing cholangitis (PSC)
- Alcoholic liver disease
- Definite autoimmune liver disease or overlap syndrome
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- Non-alcoholic steatohepatitis (NASH)
- Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN, ascites, encephalopathy, known esophageal varices or history of variceal bleeding and active or history of hepatorenal syndrome.
- History of any venous thromboembolism, transient ischemic attack (TIA), intracranial hemorrhage, neoplasm, arteriovenous malformation, vasculitis, bleeding disorder, coagulation disorders or screening blood tests that indicate altered coagulability (e.g. platelet count, activated partial thromboplastin time [aPTT], partial thromboplastin time [PTT] or thrombin time [TT] tests).
- Patients with INR > upper limit of normal (ULN) at visit 1.
- Patients with total bilirubin > ULN at visit 1 that is not due to Gilbert's syndrome
- Patients with >30% increase in ALT, total bilirubin, or Internation normalized ratio (INR) between Visit 1 to Visit 2.
- Patients with serum creatinine >ULN according to the gender at Visit 1.
- Patients with abnormal total creatine kinase (CK) OR lipase OR amylase at Visit 1.
- Unstable cardiovascular disease, including:
- unstable angina, (i.e., new or worsening symptoms of coronary heart disease within the past 3 months), acute coronary syndrome within the past 6 months, acute myocardial infarction in the past 3 months or heart failure of New York Heart Association class (III - IV) or worsening congestive heart failure, or coronary artery intervention, within the past 6 months
- history of (within prior 3 months) or current unstable cardiac dysrhythmias
- uncontrolled hypertension (systolic blood pressure [BP] >160 mmHg and/or diastolic BP >100 mmHg)
- stroke or transient ischemic attack within the prior 6 months
- History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial nonmelanoma skin cancer.
- Contraindications to Saroglitazar magnesium or has any conditions affecting the ability to evaluate the effects of Saroglitazar magnesium.
- Known allergy, sensitivity or intolerance to the study drug, comparator or formulation ingredients.
- Participation in any other clinical study within the previous 3 months of screening.
- Illicit substance abuse within the past 6 months.
- History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, human immunodeficiency virus (HIV), coronary artery disease or active gastrointestinal conditions that might interfere with drug absorption).
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Carolinas Healthcare System
Charlotte, North Carolina, 28204
Consultants for Clinical Research
Cincinnati, Ohio, 45249
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Gastrointestional Specialists of Georgia
Marietta, Georgia, 30060
Schiff Center for Liver Diseases/University of Miami
Miami, Florida, 33136
Rutgers NJ Medical School
Newark, New Jersey, 07101
California Liver Research Institute
Pasadena, California, 91105
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Einstein Medical Center Philadelphia
Philadelphia, Pennsylvania, 19141
About this study
Official title: A Phase 2, Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Tolerability and Efficacy of Saroglitazar Magnesium in Patients With Primary Biliary Cholangitis (EPICS )
prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability and efficacy of saroglitazar magnesium 2 mg, 4 mg in Patients with Primary Biliary Cholangitis (PBC). A total 36 subjects will be enrolled in a ratio of 1:1:1 to receive either saroglitazar magnesium 2 mg or saroglitazar magnesium 4 mg or placebo.
Read the detailed description
Study SARO.16.004.02 is a prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability and efficacy of saroglitazar magnesium 2 mg, 4 mg in Patients with Primary Biliary Cholangitis.
A total 36 subjects will be enrolled in a ratio of 1:1:1 to receive either saroglitazar magnesium 2 mg or saroglitazar magnesium 4 mg or placebo. The primary objective is to investigate the effect of a 16-week treatment regimen of Saroglitazar magnesium 2 mg and 4 mg on alkaline phosphatase (ALP) levels in patients with Primary Biliary Cholangitis.
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- Saroglitazar magnesium 2 mg, Saroglitazar magnesium 4 mg, Placebo Oral Tablet
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saroglitazar magnesium 2 mgDrug
Also called Not any
Saroglitazar magnesium 2 mg once daily in the morning before breakfast without food, for a period of 16 weeks.
Saroglitazar magnesium 4 mgDrug
Also called Not any
Saroglitazar magnesium 4 mg once daily in the morning before breakfast without food, for a period of 16 weeks.
Placebo Oral TabletDrug
Also called Not any
Placebo once daily in the morning before breakfast without food, for a period of 16 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Saroglitazar magnesium 2 mg | Experimental | Saroglitazar magnesium 2 mg tablet Once daily for 16 weeks Receives: Drug: Saroglitazar magnesium 2 mg |
| Saroglitazar magnesium 4 mg | Experimental | Saroglitazar magnesium 4 mg tablet Once daily for 16 weeks Receives: Drug: Saroglitazar magnesium 4 mg |
| Placebo | Placebo comparator | Placebo tablet Once daily for 16 weeks Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of a 16-week Treatment Regimen of Saroglitazar Magnesium 2 mg and 4 mg on Alkaline Phosphatase (ALP) Levels in Patients With Primary Biliary Cholangitis.
Change in ALP levels after 16 weeks of Saroglitazar magnesium 2 mg and 4 mg treatment.
Measured: Baseline and Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2017
- Study start18 Aug 2017
- Primary completion7 Aug 2020
- Study completion7 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Primary Biliary CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zydus Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Deven Parmar, MD FACP FCP, Study director, Zydus Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03112681
- Sponsor's protocol ID
- SARO.16.004
- Acronym
- EPICS
- Status last verified
- Sep 2024
- First submitted
- 10 Apr 2017
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. Epub 2009 Jun 6. No abstract available.
PubMed 19501929Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.
PubMed 19554543Vuppalanchi R, Caldwell SH, Pyrsopoulos N, deLemos AS, Rossi S, Levy C, Goldberg DS, Mena EA, Sheikh A, Ravinuthala R, Shaikh F, Bainbridge JD, Parmar DV, Chalasani NP. Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis. J Hepatol. 2022 Jan;76(1):75-85. doi: 10.1016/j.jhep.2021.08.025. Epub 2021 Sep 4.
PubMed 34487750Vuppalanchi R, Gonzalez-Huezo MS, Payan-Olivas R, Munoz-Espinosa LE, Shaikh F, Pio Cruz-Lopez JL, Parmar D. A Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Saroglitazar in Patients With Primary Biliary Cholangitis. Clin Transl Gastroenterol. 2021 Mar 26;12(4):e00327. doi: 10.14309/ctg.0000000000000327.
PubMed 33769355
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Tolerability and Efficacy of Saroglitazar Magnesium in Patients With Primary Biliary Cholangitis (EPICS )
- ClinicalTrials.gov ID
- NCT03112681
- Acronym / sponsor ID
- EPICS / SARO.16.004
- Conditions
- Primary Biliary Cirrhosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Zydus Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 18 Aug 2017 (actual)
- Primary completion
- 7 Aug 2020 (actual)
- Study completion
- 7 Aug 2020 (actual)
- First posted
- 13 Apr 2017 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability and efficacy of saroglitazar magnesium 2 mg, 4 mg in Patients with Primary Biliary Cholangitis (PBC). A total 36 subjects will be enrolled in a ratio of 1:1:1 to receive either saroglitazar magnesium 2 mg or saroglitazar magnesium 4 mg or placebo.
Detailed description
Study SARO.16.004.02 is a prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability and efficacy of saroglitazar magnesium 2 mg, 4 mg in Patients with Primary Biliary Cholangitis.
A total 36 subjects will be enrolled in a ratio of 1:1:1 to receive either saroglitazar magnesium 2 mg or saroglitazar magnesium 4 mg or placebo. The primary objective is to investigate the effect of a 16-week treatment regimen of Saroglitazar magnesium 2 mg and 4 mg on alkaline phosphatase (ALP) levels in patients with Primary Biliary Cholangitis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Saroglitazar magnesium 2 mg | Experimental | Drug: Saroglitazar magnesium 2 mgSaroglitazar magnesium 2 mg tablet Once daily for 16 weeks |
| Saroglitazar magnesium 4 mg | Experimental | Drug: Saroglitazar magnesium 4 mgSaroglitazar magnesium 4 mg tablet Once daily for 16 weeks |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletPlacebo tablet Once daily for 16 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Males or females, between 18 and 75 years of age, inclusive.
- a) Patients on therapeutic doses of Ursodeoxycholic acid (UDCA) for ≥12 months and stable therapy for ≥3 months prior to enrolment.
- OR b) Patients who are unable to tolerate UDCA, and did not receive UDCA for at least 3 months from the date of screening.
- History of confirmed Primary Biliary Cholangitis Diagnosis, based on American Association for the Study of Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice Guidelines; [Lindor 2009; EASL 2009], as demonstrated by the presence of at least≥2 of the following 3 diagnostic factors:
- ALP ≥1.67x upper limit of normal (ULN) at Visit 1 and Visit 2 and with < 30% variance between the levels from Visit 1 to Visit 2.
Key exclusion criteria (25 listed)
- Consumption of >3 units of alcohol per day (>21 units per week) if male and >2 units of alcohol per day (>14 units per week) if female for at least 3 consecutive months in the last 5 years (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor).
- History or presence of other concomitant liver diseases including:
- Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN, ascites, encephalopathy, known esophageal varices or history of variceal bleeding and active or history of hepatorenal syndrome.
- History of any venous thromboembolism, transient ischemic attack (TIA), intracranial hemorrhage, neoplasm, arteriovenous malformation, vasculitis, bleeding disorder, coagulation disorders or screening blood tests that indicate altered coagulability (e.g. platelet count, activated partial thromboplastin time [aPTT], partial thromboplastin time [PTT] or thrombin time [TT] tests).
- Patients with INR > upper limit of normal (ULN) at visit 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Saroglitazar magnesium 2 mgAlso: Not anySaroglitazar magnesium 2 mg once daily in the morning before breakfast without food, for a period of 16 weeks. | Drug | Saroglitazar magnesium 2 mg |
| Saroglitazar magnesium 4 mgAlso: Not anySaroglitazar magnesium 4 mg once daily in the morning before breakfast without food, for a period of 16 weeks. | Drug | Saroglitazar magnesium 4 mg |
| Placebo Oral TabletAlso: Not anyPlacebo once daily in the morning before breakfast without food, for a period of 16 weeks. | Drug | Placebo |
Primary outcome
Effect of a 16-week Treatment Regimen of Saroglitazar Magnesium 2 mg and 4 mg on Alkaline Phosphatase (ALP) Levels in Patients With Primary Biliary Cholangitis.
Time frame: Baseline and Week 16
Change in ALP levels after 16 weeks of Saroglitazar magnesium 2 mg and 4 mg treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19501929European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. Epub 2009 Jun 6. No abstract available.
- Background: PubMed 19554543Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.
- Results publication: PubMed 34487750Vuppalanchi R, Caldwell SH, Pyrsopoulos N, deLemos AS, Rossi S, Levy C, Goldberg DS, Mena EA, Sheikh A, Ravinuthala R, Shaikh F, Bainbridge JD, Parmar DV, Chalasani NP. Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis. J Hepatol. 2022 Jan;76(1):75-85. doi: 10.1016/j.jhep.2021.08.025. Epub 2021 Sep 4.
- Derived from this study: PubMed 33769355Vuppalanchi R, Gonzalez-Huezo MS, Payan-Olivas R, Munoz-Espinosa LE, Shaikh F, Pio Cruz-Lopez JL, Parmar D. A Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Saroglitazar in Patients With Primary Biliary Cholangitis. Clin Transl Gastroenterol. 2021 Mar 26;12(4):e00327. doi: 10.14309/ctg.0000000000000327.
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases.Link provided by the sponsor.
- Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis.Link provided by the sponsor.
- Vuppalanchi R, Caldwell SH, Pyrsopoulos N, deLemos AS, Rossi S, Levy C, Goldberg DS. Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patientsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deven Parmar, MD FACP FCP study director
Zydus Therapeutics Inc.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Saroglitazar magnesium 2 mg and Saroglitazar magnesium 4 mg in people with Primary Biliary Cirrhosis, run by Zydus Therapeutics Inc. at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of a 16-week Treatment Regimen of Saroglitazar Magnesium 2 mg and 4 mg on Alkaline Phosphatase (ALP) Levels in Patients With Primary Biliary Cholangitis. (time frame: Baseline and Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03112681, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.